National Institute of Health Dr. Ricardo Jorge
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The spread of the invasive mosquito Aedes albopictus (Diptera: Culicidae) in Portugal: a first genetic analysis
No full textBackground: Aedes albopictus, commonly known as the Asian tiger mosquito, has become one of the most invasive mosquito species. Over the last 5 decades, it has been introduced and established in various tropical and temperate regions worldwide. First reported in Europe in 1979 in Albania and later in Italy in 1990, the species is now established in 13 European Union (EU)/European Economic Area (EEA) countries and 337 regions (2023). In Portugal, Ae. albopictus was first detected in the Algarve and Penafiel regions in 2017, followed by Alentejo in 2022 and Lisbon in 2023. This mosquito species poses a significant public health risk as a vector for numerous pathogenic viruses, including dengue, Zika, and chikungunya.
Methods: Aedes albopictus collected in Lisbon in 2023 were analyzed using cytochrome c oxidase I (COX) gene sequencing to understand their genetic relationships.
Results: Our data indicate that the Ae. albopictus mosquito populations detected in three locations in Lisbon in 2023 correspond to recent but distinct introduction events.
Conclusions: Although there has been no local transmission of Aedes-transmitted viruses in mainland Portugal to date, the spread of the mosquito and increased international travel increase the risk of Aedes-borne disease outbreaks. The ongoing spread of Ae. albopictus in the country and the confirmed multiple introductions in new locations raise awareness of the need to monitor mosquito vectors to control and prevent autochthonous Aedes-borne disease outbreaks.This work was funded by the Institute of Environmental Health of the Faculty of Medicine of the University of Lisbon (ISAMB), with project references FCT UIDB/04295/2020 and UIDP/04295/2020. This work was partially funded by the MOBVEC—Mobile Bio-Lab to support first response in Arbovirus outbreaks (2023–2026) project, reference HORIZON-EIC-2022-PATHFINDEROPEN-01 under the Pathfinderopen program of the European Innovation Council (CEI), and Ph.D. fellowship reference 2022.13476.BDANA (FCT).info:eu-repo/semantics/publishedVersio
Standardized Phylogenetic Classification of Human Respiratory Syncytial Virus below the Subgroup Level
No full textA globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.N.W. has received grant funding from the Bill and Melinda Gates Foundation and Sanofi
Natural selection and recombination at host-interacting lipoprotein loci drive genome diversification of Lyme disease and related bacteria
No full textLyme disease, caused by spirochetes in the Borrelia burgdorferi sensu lato clade within the Borrelia genus, is transmitted by Ixodes ticks and is currently the most prevalent and rapidly expanding tick-borne disease in Europe and North America. We report complete genome sequences of 47 isolates that encompass all established species in this clade while highlighting the diversity of the widespread human pathogenic species B. burgdorferi. A similar set of plasmids has been maintained throughout Borrelia divergence, indicating that they are a key adaptive feature of this genus. Phylogenetic reconstruction of all sequenced Borrelia genomes revealed the original divergence of Eurasian and North American lineages and subsequent dispersals that introduced B. garinii, B. bavariensis, B. lusitaniae, B. valaisiana, and B. afzelii from East Asia to Europe and B. burgdorferi and B. finlandensis from North America to Europe. Molecular phylogenies of the universally present core replicons (chromosome and cp26 and lp54 plasmids) are highly consistent, revealing a strong clonal structure. Nonetheless, numerous inconsistencies between the genome and gene phylogenies indicate species dispersal, genetic exchanges, and rapid sequence evolution at plasmid-borne loci, including key host-interacting lipoprotein genes. While localized recombination occurs uniformly on the main chromosome at a rate comparable to mutation, lipoprotein-encoding loci are recombination hotspots on the plasmids, suggesting adaptive maintenance of recombinant alleles at loci directly interacting with the host. We conclude that within- and between-species recombination facilitates adaptive sequence evolution of host-interacting lipoprotein loci and contributes to human virulence despite a genome-wide clonal structure of its natural populations.
Importance: Lyme disease (also called Lyme borreliosis in Europe), a condition caused by spirochete bacteria of the genus Borrelia, transmitted by hard-bodied Ixodes ticks, is currently the most prevalent and rapidly expanding tick-borne disease in the United States and Europe. Borrelia interspecies and intraspecies genome comparisons of Lyme disease-related bacteria are essential to reconstruct their evolutionary origins, track epidemiological spread, identify molecular mechanisms of human pathogenicity, and design molecular and ecological approaches to disease prevention, diagnosis, and treatment. These Lyme disease-associated bacteria harbor complex genomes that encode many genes that do not have homologs in other organisms and are distributed across multiple linear and circular plasmids. The functional significance of most of the plasmid-borne genes and the multipartite genome organization itself remains unknown. Here we sequenced, assembled, and analyzed whole genomes of 47 Borrelia isolates from around the world, including multiple isolates of the human pathogenic species. Our analysis elucidates the evolutionary origins, historical migration, and sources of genomic variability of these clinically important pathogens. We have developed web-based software tools (BorreliaBase.org) to facilitate dissemination and continued comparative analysis of Borrelia genomes to identify determinants of human pathogenicity.info:eu-repo/semantics/publishedVersio
Global, regional, and national burden of mortality associated with cold spells during 2000–19: a three-stage modelling study
No full textBackground: Exposure to cold spells is associated with mortality. However, little is known about the global mortality burden of cold spells.
Methods: A three-stage meta-analytical method was used to estimate the global mortality burden associated with cold spells by means of a time series dataset of 1960 locations across 59 countries (or regions). First, we fitted the location-specific, cold spell-related mortality associations using a quasi-Poisson regression with a distributed lag non-linear model with a lag period of up to 21 days. Second, we built a multivariate meta-regression model between location-specific associations and seven predictors. Finally, we predicted the global grid-specific cold spell-related mortality associations during 2000-19 using the fitted meta-regression model and the yearly grid-specific meta-predictors. We calculated the annual excess deaths, excess death ratio (excess deaths per 1000 deaths), and excess death rate (excess deaths per 100 000 population) due to cold spells for each grid across the world.
Findings: Globally, 205 932 (95% empirical CI [eCI] 162 692-250 337) excess deaths, representing 3·81 (95% eCI 2·93-4·71) excess deaths per 1000 deaths (excess death ratio), and 3·03 (2·33-3·75) excess deaths per 100 000 population (excess death rate) were associated with cold spells per year between 2000 and 2019. The annual average global excess death ratio in 2016-19 increased by 0·12 percentage points and the excess death rate in 2016-19 increased by 0·18 percentage points, compared with those in 2000-03. The mortality burden varied geographically. The excess death ratio and rate were highest in Europe, whereas these indicators were lowest in Africa. Temperate climates had higher excess death ratio and rate associated with cold spells than other climate zones.
Interpretation: Cold spells are associated with substantial mortality burden around the world with geographically varying patterns. Although the number of cold spells has on average been decreasing since year 2000, the public health threat of cold spells remains substantial. The findings indicate an urgency of taking local and regional measures to protect the public from the mortality burdens of cold spells.
Funding: Australian Research Council, Australian National Health and Medical Research Council, EU's Horizon 2020 Project Exhaustion.This study was supported by the Australian Research Council (DP210102076), the Australian National Health and Medical Research Council (APP2000581) and the EU's Horizon 2020 Project Exhaustion (Grant ID: 820655). YGa and WH were supported by the China Scholarship Council (number 202008110182 and number 202006380055). YGu was supported by the Leader Fellowship (number APP2008813) of the Australian National Health and Medical Research Council. QZ was supported by the Natural Science Foundation of Shandong Province in China (grant ZR2021QH318) and the Shandong Excellent Young Scientists Fund Program (Overseas) (grant 2022HWYQ-055). AG was supported by the European Union's Horizon 2020 Project Exhaustion (Grant ID: 820655). JK and AU were supported by the Czech Science Foundation (project 22-24920S). VH was supported by the European Union's Horizon 2020 Research and Innovation Programme (Marie Skłodowska-Curie Grant Agreement Number 101032087), and SL was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (number APP2009866)
Vírus sincicial respiratório em crianças com menos de 2 anos: tendências nas hospitalizações e fatores de risco para doença grave – dados preliminares da rede de vigilância sentinela Portuguesa
No full textVigRSV network: Filipa Bazenga, Joana Nunes, Lídia Carvalho, Carolina Constant, Rosário Barreto, Susana Castanhinha, Rita Corte-Real, Beatriz Sousa, Margarida Freitas, Luis Miguel Silva, Florbela Cunha, Leonor Cardoso, Bruno Esteves, Regina Abreu, Ana Foles, Joana Brandão Silva, Paulo Lopes, Rita Marques, Raquel Marques, Mariana Reis, Ana Loureiro, Teresa Nunes, Eurico Jorge Gaspar, Eliana Costa, Miguel Félix, Lucília Araújo, Jorge Rodrigues, José Alves, Lina Winckler, Maria Manuel Zarcos, Carla Cruz, José Lupi, Sidónia Nunes, José Alves, Luísa Preto, Teresa Magalhães, Alberto Caldas Afonso, Manuel Magalhães, Alexandra Estrada, and Almerinda Pereira.Introduction and Objectives: Respiratory Syncytial Virus (RSV) infection is an important cause of hospitalization in children under five years. A national RSV sentinel network was set up in Portugal in April 2021. We describe the trends in RSV hospitalizations until September 2022 and identify risk factors for severe disease.
Methods: Acute respiratory infections in hospitalized children under two years were reported and tested for RSV. RSV disease severity was defined by the need for ventilation or admission to an intensive care unit. Risk ratios were used to assess the association between gender, age group, gestational age, birthweight, chronic conditions, RSV subtype and severity of disease.
Results: We detected two RSV off-season epidemics in June 2021 to February 2022 and May to September 2022. 63.3% of RSV-related hospitalizations occurred in children under six months old and 8.0% had chronic conditions. 11.0% had severe disease. Children under six months and with chronic conditions had, respectively, an 18-fold risk and a 2-fold risk of developing severe illness.
Discussion: The off-season RSV epidemics were probably triggered by the relaxation of COVID-19 physical distancing measures and immunity debt. In the first epidemic, the proportion of children with severe disease was higher than reported by previous studies, however, this result is probably overestimated due to the high proportion of cases notified by central hospitals. Age < 6 months and chronic conditions predispose to severe disease. As several factors may change the pattern of RSV activity, causing more severe outbreaks at different times, countries should implement year-round RSV surveillance systems.Introdução e Objetivos: O vírus sincicial respiratório (VSR) é uma importante causa de hospitalização em crianças com menos de cinco anos de idade. Em abril de 2021, foi implementado um sistema de vigilância sentinela de VSR em Portugal. Neste trabalho, descrevem-se tendências nas hospitalizações de VSR até setembro de 2022 e identificam-se fatores de risco para doença grave.
Métodos: Foram reportados, e testados para VSR, casos de Infeção respiratória aguda em crianças hospitalizadas com menos de 2 anos de idade. Definiu-se doença grave pela necessidade de ventilação ou de internamento em Unidade de Cuidados Intensivos. Utilizaram-se riscos relativos para avaliar a associação entre sexo, grupo etário, idade gestacional, peso à nascença, comorbilidades, subtipo de VSR e gravidade da doença.
Resultados: Detetaram-se duas epidemias de RSV fora de época, em junho 2021-fevereiro 2022 e maio-setembro de 2022. 63,3% das hospitalizações por VSR ocorreram em crianças com menos de 6 meses e 8,0% tinha comorbilidades. 11,0% desenvolveu doença grave. Crianças com menos de seis meses e com comorbilidades tiveram, respetivamente, um risco 18 e 2 vezes superior de desenvolver doença grave.
Discussão: As epidemias de VSR fora de época foram provavelmente desencadeadas pelo relaxamento das medidas de distanciamento social, no âmbito de combate à pandemia de COVID-19, e pela falta de imunidade por ausência de exposição à doença. Na primeira epidemia, a proporção de crianças com doença grave foi superior ao reportado em outros estudos, contudo, este resultado está provavelmente sobrestimado pela proporção elevada de casos notificados por hospitais centrais. Idade inferior a seis meses e comorbilidades predispõem a doença grave. Uma vez que diversos fatores podem afetar a sazonalidade de VSR, causando epidemias mais severas e em diferentes alturas do ano, recomenda-se a implementação de sistemas de vigilância contínua de VSR.Keypoints: - What is known – Respiratory Syncytial Virus (RSV) infection is an important cause of hospitalization in children under five years. Seasonal data on RSV detections have been available in Portugal since 2013-2014, however, data on RSV disease burden is sparse.
- What is added – Two RSV off-season epidemics were identified in Portugal. The off-season RSV epidemics were probably triggered by the relaxation of COVID-19 physical distancing measures and immunity debt. In the first epidemic, the proportion of children with severe disease was higher than reported by previous national studies.info:eu-repo/semantics/publishedVersio
Plano de Atividades 2024
No full textConselho Diretivo do INSA: Fernando de Almeida (Presidente), Cristina Abreu Santos (Vogal).Plano de atividades de 2024 homologado.Plano de Atividades do Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA) para o ano de 2024. O INSA é um organismo público integrado na administração indireta do Estado, sob a tutela do Ministério da Saúde. Enquanto Instituto Público de interesse estratégico nacional, tem por missão contribuir para ganhos em saúde pública, enquanto Laboratório do Estado e Laboratório Nacional de Referência. Tendo por contexto o Plano Estratégico 2024-2026 e os desafios estratégicos identificados, o Plano de Atividades para 2024, reflete as prioridades institucionais e respetivos indicadores, enquanto instrumento orientador para as atividades a desenvolver no corrente ano.info:eu-repo/semantics/publishedVersio
All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone: a multicountry two-stage time series analysis
No full textMulti-Country Multi-City (MCC) Collaborative Research Network - Portugal Joana Madureira (Environmental Health Department, Instituto Nacional de Saúde Dr Ricardo Jorge, Porto), Baltazar Nunes (Department of Epidemiology, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa)Background: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally.
Methods: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels.
Findings: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3.
Interpretation: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires.Research in context - Evidence before this study: Unprecedented wildfires have been occurring in many locations globally. Air pollution from wildfires has become a considerable public health concern, given the various adverse effects on health. According to previous research, air pollution from wildfire sources is significantly linked to an increased risk of death. To ascertain the latest evidence from Jan 1, 2000, to June 25, 2023, we did a systematic search on Google Scholar, Web of Science, and PubMed, using the following terms: (“wildfire” or “bushfire” or “fire”) and (“ozone” or “O3”) and (“mortal*” or “fatal*” or “death*” or “dead*“). The language of publications was restricted to English and Chinese. Our search yielded a small number of studies investigating the impact of wildfire-related O3 exposure on mortality. These studies showed statistically significant links between O3 from wildfires and increased hospital admissions or mortality. However, the current evidence largely originates from localised or regional studies, with a notable absence of comprehensive assessments across regions globally.
Added value of this study: To our knowledge, this study is the first to systematically evaluate the associations of short-term wildfire-related O3 exposure with daily mortality across various regions and populations globally. We collected daily counts of all-cause, cardiovascular, and respiratory deaths from up to 749 locations in 43 countries or areas between 2000 and 2016. The daily concentration of O3 from wildfire sources in study locations was estimated with a 3D GEOS-Chem model. We first examined the associations of short-term wildfire-related O3 exposure with daily mortality at the location level, and then pooled results at the country, regional, and global levels via a random-effects meta-analysis. Across all locations, we found that short-term exposure to wildfire-related O3 was associated with significant percentage increases in daily all-cause and respiratory mortality. No such significant increase was found for daily cardiovascular mortality.
Implications of all the available evidence: Based on multicountry assessment of exposure, this study presents epidemiological evidence showing an excess of deaths linked to short-term exposure to wildfire-related O3. Effective risk management is required from policy makers and public health experts, involving actions to reduce exposure to wildfires.Australian Research Council and the Australian National Health and Medical Research Council
Exploring the functional features of melon peel flour for healthier bakery products
No full textThe use of fruit by-products to develop new food products could be an advantageous approach to meet the demand for healthy foods and reduce food waste. In this study, the amino acid and mineral profiles of melon peel flour were evaluated. Non-essential/toxic elements were also determined. Furthermore, two formulations (biscuit
and muffin) were developed with 50% and 100% melon peel flour, respectively. The bioaccessibility of essential minerals in these two formulations was also determined. These innovative products presented interesting contents of amino acids and high levels of minerals, contributing significantly to daily mineral requirements, mainly magnesium (18–23%), phosphorus (13–28%), molybdenum (14–17%), and manganese (10–13%). Regarding the in vitro bioaccessibility of minerals in the developed formulations, magnesium, manganese, sodium, and phosphorus were those with the highest values (75–108%). Based on these results, melon peel has the potential to improve global food security, nutrition, economic well-being, and overall health and well-being.This work was financially supported by Foundation for Science and Technology (FCT/MES) under the project Food4DIAB (EXPL/BAA-AGR/1382/2021). This work received support from FCT/MCTES (LA/P/0008/2020 DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020 DOI 10.54499/UIDP/50006/2020, and UIDB/50006/2020
DOI 10.54499/UIDB/50006/2020), through national funds. Rita C. Alves gives thanks to FCT/MES under the CEECIND/01120/2017 contract
Microbiological quality of ready-to-eat street foods in Lisbon, Portugal
No full textStreet food sector is an important component of the food distribution system in many cities. However, foods exposed for sale on the roadside are generally associated with conditions that favors its potential microbiological contamination.
In this study, the microbiological quality of 118 ready-to-eat street foods sold in the metropolitan area of Lisbon,
Portugal was evaluated. Mesophilic aerobic bacteria, yeasts, moulds, Enterobacteriaceae and Escherichia coli were used as spoilage/hygiene indicators. Listeria monocytogenes, Salmonella spp., coagulase-positive staphylococci (CPS), Clostridium perfringens, Bacillus cereus and E. coli pathotypes implicated in gastrointestinal disease were used as food safety/hygiene indicators. Thirty-five (29.7%) of the samples were classified as satisfactory, 29 (24.6%) as questionable and 51 (43.2%) as unsatisfactory. Three samples (2.6%) were unsatisfactory/ potentially dangerous, due to the presence of the L. monocytogenes> 10^2 cfu/g and/or B. cereus> 10^5 and/or CPS> 10^4 B. cereus genes encoding causative toxins were detected in the strains isolated from two samples containing> 10^5 cfu/g. Salmonella spp., Clostridium perfringens and pathogenic E. coli were not detected in any of the examined samples. CPS was detected in 26.3% of the samples.
A significant relationship between microbiological quality and food groups, with the increase of questionable and unsatisfactory classifications for those samples including raw components, like fruits and vegetables, was observed (Fisher-Freeman-Halton=29.01, p<0.001). The obtained data highlights for the need of education and training of street-food vendors to improve the food safety management system in the place of sale.We acknowledge FCT Research Unit “GREEN-IT—Bioresources for Sustainability” (UIDB/04551/2020 and UIDP/04551/2020) for financial support.info:eu-repo/semantics/publishedVersio
Investigating p.Ala1035Val in NPC1: New Cellular Models for Niemann–Pick Type C Disease
No full textNiemann-Pick type C (NPC) is a lysosomal storage disorder (LSD) caused by pathogenic variants in either the NPC1 or NPC2 genes, which encode proteins involved in the lysosomal export of unesterified cholesterol. In patients of Western European descent, the p.Ile1061Thr variant in NPC1 is especially prevalent. However, mounting evidence has positioned p.Ala1035Val as the most common variant in Portugal and the second most prevalent variant worldwide. By analyzing 10 Portuguese NPC patients homozygous for p.Ala1035Val, we found an SNP in cis on position 858 (p.Ile858Val), which we hypothesize could have a disease-modifying effect. To address this query, we created variant-specific in vitro models of NPC by stably transducing NPC1-/- ARPE-19 cells with constructs encoding different fluorescently-tagged variants of NPC1, which we used, alongside patient-derived skin fibroblasts, to investigate lysosomal positioning and the trafficking routes elicited by p.Ile1061Thr and p.Ala1035Val (with and without the p.Ile858Val SNP in cis). Our results corroborate the previously described decrease in p.Ile1061Thr-NPC1 trafficking to the lysosome and suggest a similar, if not worse, scenario for the p.Ala1035Val variant, especially when in cis with p.Ile858Val. This is the first reported functional study addressing the impact of the p.Ala1035Val variant at the cellular level, paving the way for novel therapeutic options.This research was funded by national funds through Fundação para a Ciência e a Tecnologia, I. P. (FCT), within the scope of the project EXPL/BTM-TEC/1477/2021. This work was also financially supported with funding from FCT/MCTES, through national funds (UIDB/00211/2020)